The incredible diversity and abundance of the human microbiome has only come to light in the last decade. The scientific community has learned that the gut microbial ecosystem has a major role in the development and homeostasis of the immune system. Our team wants to learn how these systems communicate to shape HIV vaccine immune responses. We are interested in how the microbiome shapes immune responses to HIV vaccines and contributes to vaccine response heterogeneity. We have a special emphasis on investigating the durability and class of antibodies that are elicited by different vaccines and the cellular responses that may contribute to these humoral endpoints, and how specific microbiota may contribute to these different responses. We will conduct correlates analyses with clinical and mouse microbiome and immunogenicity data; we will unravel mechanisms of immunity by perturbation of the immune system and the microbiome ? the immune system via multiple adjuvanted immunization regimens and the microbiome by gut microbial reconstitution in germ free mice; and we will conduct metabolomics case-control analyses from select human and mouse samples. The knowledge gained in the end will shed light on the mechanisms of how vaccines work and may improve vaccines by way of novel adjuvant discovery.